Extended release naltrexone vs buprenorphine

A recent randomized clinical noninferiority trial from Norway found that extended-release naltrexone was as noninferior to (and seemingly superior to) buprenorphine-naloxone in maintaining short-term abstinence from heroin (see doi:10.1001/jamapsychiatry.2017.3206).

Details:
--159 people were randomized to daily oral flexible-dose buprenorphine-naloxone (4-24 mg/d, target dose 16 mg/d) vs extended-release naltrexone 380mg intramuscularly every 4 weeks, for 12 weeks
--mean age 36, 28% women, 90% white, 85% intravenous users, 3% HIV positive, 55% hepatitis C seropositive, approx 7 years of substance use
--all patients went through an inpatient detox program (or were in prison/off drugs) for at least 7 days prior to starting the study
--weekly drug testing

Results:
--mean daily dose of buprenorphine was 11 mg/d
--105 people (66%) completed the study (attended all scheduled appointments, took meds as prescribed)
--retention rate for naltrexone was non-inferior to buprenorphine, with mean time of 69 vs 64 days for naltrexone vs buprenorphine
--total number of opioid-negative urine tox screens and use of heroin or other opioids (typically pills), all non-inferior
--and, superiority analysis in fact found that naltrexone was associated with significantly lower use of heroin and other illicit opioids:
    -- % of opioid-negative urines was 90% with naltrexone vs 80% with buprenorphine (p<0.001, for difference)
     --days of use of heroin: 3.2 fewer with naltrexone (P<0.001), approx 1 vs 4. Days of use of other drugs was pretty low: other illicit opioids (2 days for naltrexone vs 4 days for buprenorphine), cannabis (7 vs 5), amphetamines (3 vs 2), cocaine (0.5  for each), benzos (7 vs 7), alcohol for intoxication (3 vs 2) [but, only 66% completed the study, a select group]
--secondary outcomes: no difference in use of amphetamines, cocaine, alcohol, cannabis, or injecting drugs, but there was significantly higher use of benzos in the naltrexone group
--there was less heroin craving with naltrexone than buprenorphine, and more patient satisfaction with naltrexone (especially at week 4 and 8, less so at week 12)
--adverse events: 69% for naltrexone vs 35% for buprenorphine; serious ones 9 vs 4% (mostly withdrawal-related for naltrexone), insomnia (11% vs 4%), anxiety (17% vs 8%) and injection site problems (6% vs 0). Overall 39% on naltrexone had some withdrawal-related symptoms vs 14% on buprenorphine

Commentary:
--this is the first trial i have seen which directly compares IM naltrexone vs buprenorphine.  Given the decreased toxicity of buprenorphine over methadone, as well as primary care prescribing restrictions on the latter, buprenorphine is the usual OMT (opioid medication treatment) in primary care in the US; and it is the preferred drug in many other countries
--oral naltrexone has been used in the past, but has been plagued with low adherence rates, high dropout rates, and even increased mortality in one study
--the potential advantages of the extended-release naltrexone injections include its not being an opioid med, that there is no real potential for diversion, that it should provide prolonged periods of abstinence (given that it is an opioid antagonist that competitively blocks opioid receptors), and it lasts a month.
--those who completed this trial will be offered treatment for 48 weeks, which data will be presented subsequently

so,
--finally a head-to-head trial, which pretty clearly shows extended-release injectable naltrexone to be at least as good as buprenorphine-naloxone, with less illicit opiate use, less craving, and more patient satisfaction.  And, this is despite more associated adverse effects. Though it should be noted that 1/3 of the enrolled patients overall in this study did drop out.
--i am personally pretty encouraged by this study.  My experience with buprenorphine has been very positive, with half the patients sailing through without using opiates and maintaining pretty normal lives (home life, work life, etc). And most of the remaining half doing basically well with some transient problems (after all, they do usually still live in the same environments with the same social stressors and inducements leading to the opiate use in the first place). It will be useful to see the longer-term followup from this study, and perhaps some confirmatory studies. But this study reinforces that there is another quite reasonable alternative to buprenorphine/naloxone for some patients.

for some relevant prior blogs on buprenorphine, see http://gmodestmedblogs.blogspot.com/search/label/buprenorphine , with a recent one on increasing opioid use in adolescents/young adults but only a quarter of whom were prescribed buprenorphine or naltrexone